Cyclic neutropenia, or cyclic hematopoiesis, is a disease of man and grey collie dogs caused by a defect in the regulation of blood cell formation. On the basis of bone marrow transplant experiments, it is presumed to be a disease of the hematopoietic stem cells. Recent studies have indicated that canine cyclic hematopoiesis can be corrected by chronic endotoxin administration and oral lithium therapy, in addition to marrow transplantation. In the proposed research, we will extend our studies on the regulation of hematopoiesisin grey collies using in vivo and in vitro techniques. We anticipate that more precise delineation of the marrow defect in this disorder will provide new insights into the regulation of hematopoiesis and may suggest new therapies for this and related diseases.